Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 140, Issue -, Pages 92-103Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.09.003
Keywords
Indole; Anti-inflammatory activity; Lipopolysaccharide; Tumor necrosis factor-alpha; Interleukin-6; Nitric oxide
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Funding
- Council of Scientific and Industrial Research (CSIR), New Delhi [02(0203)/14/EMR-II]
- SERB-DST New Delhi [EMR/2015/001548]
- CSIR
- DST-INSPIRE, New Delhi
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The conjugates obtained by the combination of indole and aminophenyl morpholinone were screened for TNF-alpha and IL-6 inhibition in microglial cells. Compound 4 was found to be the most potent anti-inflammatory agent as it reduced LPS induced level of inflammatory cytokines TNF-alpha and IL-6 by 71% and 53%, respectively. A significant decrease in NO and MMPs release from BV2 cells in culture pretreated with this compound as well as inhibition of nuclear translocation of NF-kappa B and AP-1 was observed. 75% inhibition of acetic acid induced algesia in swiss albino mice was noticed in the presence of compound 4. Experimental data and molecular docking studies indicate that the compounds are targeting TNF-alpha, iNOS and IL-6. (C) 2017 Elsevier Masson SAS. All rights reserved.
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